tbuckley/cabot-search huggingface dataset:
MELODY (Methods for Localization of Different Types of Breast Lesions): A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).
Authors: Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Isabel T. Rubio, Jana de Boniface, Nina Ditsch, Andreas Karakatsanis, Rajiv V Dave, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Walter Paul Weber, Natalia Krawczyk, Steffi Hartmann, Guldeniz Karadeniz Cakmak, Markus Hahn, Michael Patrick Lux, Marjolein Smidt, Neslihan Cabioglu, James Harvey
Journal: Journal of Clinical Oncology (2023)

TPS626 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com ). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 20 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Clinical trial information: NCT05559411 .
Informative tools to optimize neoadjuvant therapy in ER positive, HER2 negative breast cancers.
Authors: Lidiya Luzhna, Stephen Chia, Mehrnoosh Pauls, Nathalie LeVasseur
Journal: Journal of Clinical Oncology (2023)

e12595 Background: Neoadjuvant therapy (NAT) in HR+/HER2- tumors is often disputable. While the role of Oncotype DX has been well established in adjuvant settings, its clinical utility and potential implementation for prediction of NAT benefit requires further study. This ongoing study aims to report the feasibility of Oncotype DX testing on core biopsy specimens prior to NAT in patients with operable HR+/HER2- breast cancer. The effect of the recurrence score (RS) on systemic treatment recommendations and its correlation to dynamic markers of proliferation and NAT response will be evaluated. Methods: Participants with clinical T2-T4 and/or node positive HR+/HER2- breast cancer had Oncotype DX testing done prior to NAT. Clinico-pathological information, treatment regimens, clinical, radiologic, and pathological responses were recorded. Results: Of the 48 patients with HR+/HER2- breast cancer referred to BC Cancer Vancouver for consideration of NAT between September 2021 and January 2023, 26 were eligible and enrolled in the study. The success rate of the Oncotype DX on core biopsy samples was 96%. The mean turnaround time from patient consent to RS report was 19 calendar days. Approximately 32% of tumors had a RS equal or higher than 26 while 4% had a score less than 10. Nearly 25% of neoadjuvant treatment recommendations were changed based on the RS. Overall, 33% of patients received neoadjuvant chemotherapy, 54% received neoadjuvant endocrine treatment, and 12.5% proceeded with upfront surgery. Conclusions: The success rate of Oncotype DX testing on core biopsy samples was excellent. There were multiple factors that influenced trial enrollment, highlighting the low uptake and equipoise of NAT use in HR+/HER2- tumors. The Oncotype DX testing resulted in a change in systemic treatment plan in 25% of patients. Analyses are ongoing to correlate the recurrence score to NAT response, dynamic Ki-67 changes and breast MRI changes. Clinical trial information: NCT03790813 .
Advanced deep-learning algorithm for multi-cancer detection using cf-WGS.
Authors: Tae-Rim Lee, Eunhae Cho, Junnam Lee, Jin Mo Ahn, Dasom Kim, Chang Seok Ki, Minsoo Kim, Jae Sung Lee, Ji Hye Sohn, Sook Ryun Park, Ki Byung Song, Eunsung Jun, Dongryul Oh, Jeong-Won Lee, Young Sik Park, Gi-Won Song, Jeong-Sik Byeon, Bo Hyun Kim
Journal: Journal of Clinical Oncology (2023)

e13560 Background: Applying machine learning in circulating cell-free DNA (cfDNA) whole genome sequencing (WGS) holds the potential to be a valuable tool for early cancer detection. However, unless the batch effect is taken into account, detecting very tiny cancer signals involves an overfitting issue with relatively small training sample number for artificial intelligence training. This study aimed to develop advanced deep-learning model for cancer detection from cfDNA whole genome sequencing data with minimal batch effect. Methods: We generated low depth cfDNA whole genome sequencing data from 412 cancer patients and 1,269 healthy individuals. The size and end motif frequency of each fragment was measured and represented as a two-dimensional matrix. Each sample data was normalized with reference samples in the same batch prior to model training to remove batch effects between sequencing runs and was divided into 4 datasets stratified by sequencing batch for cross-validation of the models. The final model combines a grouped convolution neural network (CNN) and a long short-term memory (LSTM) model for sequential size information training. Results: The model showed an accuracy of 93.1% and an AUC of 0.97. With a 95% specificity threshold, the model showed an overall sensitivity of 87% and a precision of 84.7%. For individual cancer types, liver, ovarian, esophageal, pancreatic, and lung showed sensitivities of 94.4%, 81.1%, 85.6%, 100%, and 78.2%, respectively. For cancer stages, the sensitivity was 78.6% in stage I, 86.5% in stage II, 91.5% in stage III, and 92.7% in stage IV at 95% specificity threshold. Conclusions: The deep learning models trained using fragment size and end motif frequency of cfDNA demonstrated promising results for cancer detection. The improved performance of this model highlights the potential for improving cancer detection by incorporating advanced deep learning algorithm with well curated training data for batch effect correction.
The impact of exercise training on the pathologic response and tumor immune microenvironment in breast cancer after neoadjuvant chemotherapy: An exploratory study.
Authors: Helena Guedes, David João, Pedro Antunes, Sandra Silva, Inês Leão, Dulce Esteves, Luisa Helguero, Telma Costa, Sofia Viamonte, Alberto Alves, Margarida Caldas, Ana Joaquim
Journal: Journal of Clinical Oncology (2023)

e12596 Background: In early breast cancer (BC), pathological complete response (pCR) is an efficacy endpoint of neoadjuvant chemotherapy (ChT) and percentage of tumor-infiltrating lymphocytes (TILs) is a prognostic biomarker. Although exercise training is an evidence-based supportive care across the BC journey, one open question is its impact on the antitumor effect of neoadjuvant ChT. The authors aim to investigate the effects of a supervised exercise training program (STEP) in pCR and TILs in BC women undergoing neoadjuvant ChT. Methods: MAMA_MOVE_Gaia on Treatment (ISRCTN, ISRCTN32617901) is randomized controlled trial in which women with early BC undergoing anthracycline containing ChT were randomized in a 1:1 ratio to a SETP or to usual care, close to recruitment in January 2022. For this exploratory analysis, we retrospectively identified patients who underwent neoadjuvant ChT, and compare pCR and TILs between the two arms. Results: Sixty-four participants were included, aged from 26 to 72 years old (mean = 50.3, SD = 10.1) majority with stage II and III (n = 58, 90,6%) and HER2+ (n = 23, 35.9%) or triple negative (n = 19, 29.7%) disease. The pCR in STEP arm had a prevalence of 56.7% and in the usual care arm of 55.9%(p = 0.950). In the STEP arm median TILs were, for the biopsy and tumor site, of 5.0 (range 0.0-80.0) and 5.0 (range 5.0-30.0). In the usual care arm, median TILs were, for the biopsy and tumor site, of 5.0 (range 0.0-90.0) and 0.0 (range 0.0-30.0). There was no difference between groups for TILs of the biopsy (p = 0.907). Higher TILs of the tumor site was marginally associated with the STEP arm (p = 0.082). Conclusions: Despite the results obtained, it is believed that a larger sample may lead to different results. However, these data could also support future research in this field, bringing new insights for cancer survivors continuum of care.
Sociodemographic and clinicopathologic factors of triple negative breast cancer at an academic urban safety-net hospital.
Authors: Judy Jiaqi Wang, Brendin Beaulieu-Jones, Jose Acevedo, Lauren Oshry, Andrea Merrill, Michael Ryan Cassidy, Naomi Yu Ko
Journal: Journal of Clinical Oncology (2023)

1090 Background: Racial disparities in breast cancer in the United States is a persistent and ongoing problem. Decades of research is derived from large population based data sets and little is published with granular detail of specific, actionable factors to target for interventions. From a large urban safety-net hospital, we evaluate sociodemographic and clinicopathologic factors on survival outcomes of triple negative breast cancer. Methods: We conducted a single-institution retrospective study of patients with invasive breast cancer, diagnosed and treated between January 2010 and December 2021 at an academic safety-net hospital where insurance systems allow for access and treatment for all patients. Demographic, tumor and treatment characteristics were obtained. Chi-square and ANOVA were used to examine associated factors among White, Black, and other races. Survival was analyzed using the Kaplan-Meier estimator and log-rank test. Significant risk factors were identified with Cox regression analysis. Results: 251 women with invasive triple negative breast cancer were diagnosed and treated during the study period. Median age was 58 years, 68.9% were non-white, and 64.9% were publicly insured or uninsured patients. Median time from diagnosis to treatment initiation was 29 days and follow up period was 1392 days. Having a non-English primary language and living in areas with lower socioeconomic indices are observed in non-White patients (P=0.003, 0.033) and predictive of a higher clinical stage at presentation (P=0.011, 0.021). Black patients were diagnosed at higher histologic grade (Black: 82.4%, White: 79.7%; P=0.003) and White patients were more likely to change facility during the treatment course (White: 32.4%, Black: 16.03%; P=0.005). No significant racial disparities were observed in time to treatment, recurrence rate, and overall survival. Among patients indicated for adjuvant therapies, including chemotherapy, immunotherapy, and radiation, rates of recommendation and completion of therapy did not vary by race. Five year survival did not significantly vary by race when adjusted for demographic and clinicopathologic factors. Conclusions: At an academic urban safety-net hospital where access to diagnostic and treatment resources are comparable across patient populations, no racial disparities were seen in treatment, recurrence, and survival outcomes. Further research on racial differences in breast cancer biology and health behaviors may improve understanding of triple negative disease or mitigate later stage diagnosis.
Shifting trends in the usage of trastuzumab with its biosimilar inception in India.
Authors: Nagendra Ramanjinappa, Kunvar Harsh Upveja, Jatin Agarwal
Journal: Journal of Clinical Oncology (2023)

e13037 Background: Biosimilars have the potential for cost savings and thus help increase access to treatment. The first trastuzumab biosimilar was introduced in 2014 in India. A qualitative study was conducted focusing on understanding the physicians’ perceptions on using trastuzumab biosimilars in HER2+ breast cancer (BC) and changes in trends from pre-biosimilar to post-biosimilar era in India. These study results were presented at ESMO Asia 2022 conference (https://www.annalsofoncology.org/article/S0923-7534(22)04219-3/fulltext). The current abstract utilizes sales data on trastuzumab to reexamine trends in biosimilar usage in this indication in India. Methods: Trends in patients treated with trastuzumab innovator or biosimilar were identified using data from Ipsos’ India Oncology Sales Audit (Jan 2014-Dec 2020), which reports Net Realized Value of all brands marketed by ~60 oncology companies across India. Data were collected using open-source intelligence and telephone interviews with sales/marketing personnel from pharmaceutical companies and distributors. The number of patients treated with trastuzumab was calculated using Microsoft Excel based on their body weight (assumed to be 60 kg), completing 6 months (9 cycles) of therapy and consuming 1 vial of 440 mg/cycle (8 mg/kg loading dose and 6mg/kg maintenance dose Q3W). Results: Approximately 68,000 HER2+ BC patients received trastuzumab from 2014-2020, out of which 46,000 received biosimilars and 22,000 innovators. Eighteen percent of patients were treated with biosimilars in 2014 which increased to 88% by end of 2020. There was a 17% decline in patients treated with innovator from the year 2017-2018, whereas patients treated with biosimilars grew by 229% in the same period, due to the launch of multiple biosimilars in this era. In the year 2020, there was a 15% decline (13% for biosimilar vs 30% for innovator) in the overall number of patients receiving trastuzumab which was primarily due to the impact of COVID-19. Similarly, pertuzumab usage increased 17 times from its introduction in 2015 till 2020. There has been decline in innovator trastuzumab patients and increase in the number of patients treated with biosimilar trastuzumab and pertuzumab in the last seven years; supporting our physician perception survey, wherein oncologists used pertuzumab with biosimilars in almost 45% of their patients. Conclusions: Findings from this data coincide with the physician perception survey suggesting increasing trend in usage of biosimilars in the last seven years. Biosimilars are preferred option amongst oncologists in India because of affordability and accessibility. The availability of quality biosimilars has the potential to reduce health care expenditure, and an effective supply also increase patient’s adherence to treatment.
Comprehensive genomic profiling of Taiwanese patients with breast cancer using a novel targeted panel: Preliminary analyses from a prospective triple-negative cohort.
Authors: Chi-Cheng Huang, Yi-chen Yeh, Hsiang-Ling Ho, Chun-Yu Liu, Yi-Fang Tsai, Ling-Ming Tseng
Journal: Journal of Clinical Oncology (2023)

e12553 Background: Breast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database to improve treatment outcomes. This study aims to determine the molecular alterations and identify potential therapeutic targets from a cohort of Taiwanese triple negative breast cancers using a novel next-generation sequencing (NGS) targeted panel. Methods: The VGH-TAYLOR study was designed to understand the genetic profiling of different subtypes of breast cancer in Taiwan. The study population comprised both early- (first-line surgery or neoadjuvant therapy) and late-stage (early/late relapse or de novo stage IV disease) of breast cancers, and we conducted molecular profiling with the illumina TruSight Oncology 500 assay using both DNA and RNA extracted from FFPE tissues from a subset of 101 prospectively enrolled breast cancers, which were previously assayed with a commercialized panel of 161 genes. Results: A total of 100 breast cancers from VGH-TAYLOR study were successfully assayed, with the majority (n = 97) being triple-negative, two HER2 over-expressed and the remaining one being HER2-low phenotypically. The most prevalent actionable alterations (more than 5% of study cohort) came from BRCA2 (24%), BRCA1 (12%), PALB2 (5%), PIK3CA (38%, both mutations and amplifications), ERBB2 (14%, both mutations and amplifications), ERBB3 (10%) and PTEN (12%). One-quarter of assayed samples were categorized into tumor mutation burden (TMB)-high cancers ( &gt; 10 mutations per million bases), which came from 15 out of 74 (20%) early-stage and 10 out of 26 (38%) late-stage patients (chi-square test p-value: 0.06). In general, the novel panel with 500 targeted genes reported more actionable alterations than the former one with limited interrogated genes ( BRCA2: 7%, BRCA1: 12%, PALB2: 7%, PIK3CA: 45%). Conclusions: Our study ascertained the clinical applicability and feasibility of comprehensive genomic profiling from a cohort of Taiwanese breast cancers. Overall, the successful rate for NGS with QC metrics are around 90%. The novelty benefits from more investigated genes as well as multi-gene biomarkers such as TMB and microsatellite instability (MSI) status. Patients with a positive finding from the genomic assay may benefit from an immune checkpoint inhibitor (TMB-high and MSI), poly ADP- ribose polymerase (PARP) inhibitor (homologous recombination deficiency genes: BRCA1/2 and PALB2), selective estrogen receptor degrader ( ESR1), tyrosine kinase inhibitor ( ERBB2/3), phosphoinositide 3-kinase inhibitor ( PIK3CA) and so on. Further studies with more samples enrolled and longer follow up are warranted to elucidate the true value of comprehensive genomic profiling for breast cancer.
BPI-16350, a novel promising CDK4/6 inhibitor for HR+/HER2- metastatic breast cancer (MBC): Results from a phase I study.
Authors: Jian Zhang, Rujiao Liu, Shuiping Gao, Wenyan Chen, Xinghua Han, Yanjie Ma, Lieming Ding, Jiabing Wang, Hong Lan, Xichun Hu
Journal: Journal of Clinical Oncology (2023)

e13051 Background: BPI-16350 is a highly potent CDK4/6 inhibitor, and has a similar structure to abemaciclib but with less inhibition of CDK9 in pre-clinical experiments. This is an open-label, dose-escalation and -expansion phase I study to evaluate the safety, pharmacokinetics, and preliminary antitumor activity of BPI-16350 as monotherapy (Part A) and combined treatment with fulvestrant (FUL) in pts with HR+/HER2- MBC (Part B). Methods: In Part A, patients (pts) who had failed standard therapies were eligible to receive BPI-16350 in a standard 3+3 pattern at doses ranging from 50−500 mg QD. In Part B, BPI-16350 (300 mg or 400 mg QD) plus intramuscular FUL was administered in pts who had experienced secondary endocrine resistance. Pts in this part should have received no more than one line of chemotherapy for metastatic disease and no prior therapies with other CDK4/6 inhibitors, FUL or everolimus. Results: As of 13 November 2022, 24 pts were enrolled in Part A (50 mg, n=4; 100 mg, n=4; 200 mg, n=3; 300 mg, n=3; 400 mg, n=4; 500 mg, n=6), including 23 pts with MBC and one pt with abdominal liposarcoma. 66.7% (16/24) of pts had received ≥ 2 lines of chemotherapies and 70.8% (17/24) had received ≥ 2 lines of endocrine therapies. Only one dose-limiting toxicity event (i.e. Grade 3 blood creatinine increased) was observed at 500 mg dose, and the maximum tolerated dose was not reached. Grade ≥ 3 AEs occurred in 45.8% (11/24) of pts, with the most common being diarrhea (4/24), anemia (3/24), and neutropenia (2/24). The median time to peak concentration for BPI-16350 was 2.0-17.0 hours, and the mean half-life was 35.6-51.0 hours, supporting once-daily dosing. After a single oral dose of 50–500 mg of BPI-16350, the drug exposure was dose-proportional. With a QD dosing regimen, accumulation was 2.1–3.3 fold. The disease control rate (DCR) was 70.8% (17/24, 95% CI: 48.9%-87.4%). One pt (4.2%) achieved a partial response at 500 mg dose. In Part B, 46 pts with HR+/HER2- MBC were enrolled (300 mg, n=9; 400 mg, n=37), and 63.0% (29/46) of pts were still on treatment. Grade ≥ 3 AEs occurred in 42.5% (20/46) of pts, with the most common being anemia (8/46), leukopenia (6/46), hypokalemia (6/46), and neutropenia (5/46). Among the 46 pts, 43 pts were evaluable for efficacy. The DCR was 97.7% (42/43, 95% CI: 87.7%-99.9%). The confirmed overall response rate was as high as 60.5% (26/43, 95% CI: 44.4%-75%). The median progression-free survival has not been reached (95% CI: 11.1 months–not reached). Conclusions: To our knowledge, BPI-16350 plus FUL demonstrated numerically highest antitumor activity compared with the already approved CDK4/6 inhibitors and less Grade ≥ 3 diarrhea than abemaciclib. A phase III study (NCT05433480) comparing BPI-16350 plus FUL versus placebo plus FUL in pts with MBC is ongoing. Clinical trial information: NCT03791112 .